COVID-19 Respiratory Failure: Targeting Inflammation on VV-ECMO Support.

The outbreak of novel coronavirus (SARS-CoV-2) that causes the respiratory illness COVID-19 has led to unprecedented efforts at containment due to its rapid community spread, associated mortality, and lack of immunization and treatment. We herein detail a case of a young patient who suffered life-threatening disease and multiorgan failure. His clinical course involved rapid and profound respiratory decompensation such that he required support with venovenous extracorporeal membrane oxygenation (VV-ECMO). He also demonstrated hyperinflammation (C-reactive protein peak 444.6 mg/L) with severe cytokine elevation (Interleukin-6 peak > 3000 pg/ml). Through treatment targeting hyperinflammation, he recovered from critical COVID-19 respiratory failure and required only 160 hours of VV-ECMO support. He was extubated 4 days after decannulation, had progressive renal recovery, and was discharged to home on hospital day 24. Of note, repeat SARS-CoV-2 test was negative 21 days after his first positive test. We present one of the first successful cases of VV-ECMO support to recovery of COVID-19 respiratory failure in North America.

Radiology Report Template Optimization at an Academic Medical Center.

OBJECTIVE. Variability in reports of the same imaging study performed at the same institution may be confusing to referrers and patients, hindering results communication. The purpose of this study was to introduce a quality improvement initiative aimed at reducing variation in radiology report templates at a large academic center. MATERIALS AND METHODS. The quality improvement initiative was undertaken at a large multisite, multidivision academic radiology practice performing more than 820,000 radiologic examinations annually. A project charter defined the goals, scope, and personnel of the initiative and an escalation pathway for conflict resolution. Standard requirements for templates were initially developed. From September 2017 to May 2018, an oversight committee (24 organ system and modality-based work groups with representatives from nine subspecialty divisions) reviewed and harmonized all institutional radiology report templates across the enterprise irrespective of the imaging site or division that interpreted the study. The primary outcome measure was percentage reduction in report templates after harmonization. The secondary outcome measure was monthly adherence to harmonized templates for 9 months after implementation assessed by manual review of 40 randomly selected reports per month. The paired t test was used to assess template reduction, and the chi-square trend test was used to study trend in adherence to harmonized templates. RESULTS. Among 19,687 total templates at baseline, 597 harmonized templates remained after harmonization (p < 0.001). There was variation in template reduction by work group (multiple p < 0.05; reduction range, 79.2-99.3%). Radiologist adherence to harmonized templates ranged from 88.0% to 100%, unchanged in the 9 months after implementation (p = 0.23, chi-square trend). CONCLUSION. A radiology report harmonization initiative reduced 97.0% of report templates with a sustained high degree of adherence to harmonized templates after implementation at a large multisite multidivision academic radiology practice.

An Electronic Health Record Order Entry-Enabled Educational Intervention Is Not Effective in Reducing STAT Inpatient Radiology Orders.

OBJECTIVE: Assess whether introducing order priorities with defined performance expectations in the electronic health record (EHR) reduces immediate inpatient radiology orders. MATERIALS AND METHODS: This Institutional Review Board-approved, retrospective study was performed at a 776-bed academic hospital conducting 164,000+ inpatient radiology examinations annually. Study period was January 2, 2017, to July 23, 2017; 14 weeks pre- and postimplementation of an education-only intervention including replacing urgent and as soon as possible priorities with imaging within next 6, 12, or 24 hours; imaging in the morning; and required for discharge priorities. STAT routine, timed, today order priorities remained unchanged. Institution-wide training immediately pre- and postimplementation was provided through two waves of e-mail and electronic tip sheets. Primary outcome measure was total STAT studies ordered of total radiology studies ordered per week (STAT rate). Secondary outcomes were non-STAT, non-routine (non-SR) order rate, and routine order rate. Paired t test and statistical process control (SPC) analysis were performed. RESULTS: STAT rate pre- (22.5%, 7,150 STAT of 31,765 total; weeks 1-14) and postintervention (23.4%, 7,481 STAT of 32,034 total; weeks 16-29) remained unchanged (P = .37). SPC demonstrated no special cause variation. Postintervention non-SR rate increased 3-fold (2.7%, 859 non-SR of 31,765 total pre-intervention versus 8.2%, 2,615 non-SR of 32,034 total postintervention; 8.2%/2.7% = 3.0; P < .0001). There was an 8.8% relative reduction in routine rate postintervention (73.9%, 23,471 routine of 31,765 total pre-intervention; 67.4%, 21,579 routine of 32,034 total postintervention; (73.9% - 67.4%)/73.9% × 100 = 8.8%; P < .0001). CONCLUSION: Implementing ordering priorities with defined performance expectations in the EHR reduced routine but did not reduce STAT inpatient radiology orders. More stringent interventions may be needed to reduce unnecessary STAT inpatient radiology ordering to improve use of limited imaging resources.

Improving Radiology Peer Learning: Comparing a Novel Electronic Peer Learning Tool and a Traditional Score-Based Peer Review System.

OBJECTIVE: The purpose of this study was to compare the yields of peer learning between a radiology electronic peer learning tool (PLT) and a score-based peer review (SBPR) system. MATERIALS AND METHODS: This retrospective study was performed from May 1, 2017, through October 31, 2017, at a 776-bed academic hospital performing more than 620,000 radiology examinations annually. Use of a PLT that generates alerts facilitating closed-loop feedback was initiated on March 1, 2017. Functions included providing peers with the following: clinical follow-up after review of prior reports, positive feedback, and consultation to solicit second opinions. In the same period, an SBPR system yielded the following scores: 1, agree with original interpretation; 2, minor discrepancy; 3, moderate discrepancy; and 4, major discrepancy. Potential learning opportunities were defined as cases receiving a clinical follow-up alert (PLT system) and reports scored 3 or 4 (SBPR system). Primary outcome was clinically significant feedback per total reports reviewed, measured as radiology report addendum rate (number with addenda divided by number of reports reviewed monthly for each system). The secondary outcome was potential learning opportunity rate (number of clinical follow-up alerts or reports scored 3 or 4 divided by the total number of radiology reports reviewed monthly). A paired t test was used for statistical analysis. RESULTS: The overall PLT report addendum rate was 11.2% (23 addenda/206 reports) versus 0.27% (13 addenda/4861 reports) for SBPR (p = 0.03), a 41-fold difference (11.2/0.27). The potential learning opportunity rate for PLT was 50.0% (206 clinical follow-up alerts among 412 total alerts) versus 0.53% (26 scored 3 or 4 among 4861 reports reviewed) for SBPR (p = 0.00003), a 94-fold difference (50/0.53). CONCLUSION: A PLT improves radiology peer learning with a significantly higher yield of clinically significant feedback and potential learning opportunities compared with a traditional SBPR system.

Yield of Learning Opportunities From a Radiology Random Peer Review Program.

OBJECTIVE: The purpose of this study is to assess the yield and usage of a radiology random peer review program in identifying potentially meaningful discrepancies in radiology reports that could serve as learning opportunities. MATERIALS AND METHODS: This retrospective study was performed at a 776-bed tertiary academic hospital that renders more than 620,000 radiology reports annually. A workstation-embedded peer review system was implemented on January 1, 2014, followed by radiologist training over the next 12 weeks. From April 1, 2014, through September 30, 2017 (14 quarters), randomly selected radiologic studies were peer reviewed and scored as follows: 1, agree with original interpretation; 2, minor discrepancy, not likely clinically significant; 3, moderate discrepancy, may be clinically significant; or 4, major discrepancy, likely clinically significant. Reports scored as 3 or 4 were defined as having potentially meaningful discrepancies, and the discrepancy type was characterized. The primary outcome was the quarterly rate of potentially meaningful discrepancies. The secondary outcome was program usage rate (number of reports peer reviewed / total reports generated). Chi-square trend test assessed changes in outcomes over time. RESULTS: Of a total of 42,891 peer reviews performed, the overall potentially meaningful discrepancy rate (or yield) was 0.5% (233/42,891). The quarterly potentially meaningful discrepancy rate decreased significantly over the study period (p < 0.0001). The quarter 14 potentially meaningful discrepancy rate (0.003) was 70% lower than the quarter 1 rate (0.011). Quarterly program usage also decreased significantly over the study period (p < 0.0001). Quarter 14 usage (0.015) was 56% lower than quarter 1 usage (0.034). Among 184 potentially meaningful discrepancy reports that could be categorized, the most common discrepancy type was error of perception (87/184). CONCLUSION: A workstation-embedded random radiology peer review program had a very low yield in identifying learning opportunities and declining usage over time.

Bladder cancer diagnosis with CT urography: test characteristics and reasons for false-positive and false-negative results.

PURPOSE: To determine test characteristics of CT urography for detecting bladder cancer in patients with hematuria and those undergoing surveillance, and to analyze reasons for false-positive and false-negative results. METHODS: A HIPAA-compliant, IRB-approved retrospective review of reports from 1623 CT urograms between 10/2010 and 12/31/2013 was performed. 710 examinations for hematuria or bladder cancer history were compared to cystoscopy performed within 6 months. Reference standard was surgical pathology or 1-year minimum clinical follow-up. False-positive and false-negative examinations were reviewed to determine reasons for errors. RESULTS: Ninety-five bladder cancers were detected. CT urography accuracy: was 91.5% (650/710), sensitivity 86.3% (82/95), specificity 92.4% (568/615), positive predictive value 63.6% (82/129), and negative predictive value was 97.8% (568/581). Of 43 false positives, the majority of interpretation errors were due to benign prostatic hyperplasia (n = 12), trabeculated bladder (n = 9), and treatment changes (n = 8). Other causes include blood clots, mistaken normal anatomy, infectious/inflammatory changes, or had no cystoscopic correlate. Of 13 false negatives, 11 were due to technique, one to a large urinary residual, one to artifact. There were no errors in perception. CONCLUSION: CT urography is an accurate test for diagnosing bladder cancer; however, in protocols relying predominantly on excretory phase images, overall sensitivity remains insufficient to obviate cystoscopy. Awareness of bladder cancer mimics may reduce false-positive results. Improvements in CTU technique may reduce false-negative results.

Fetal ovarian cysts: review of imaging spectrum, differential diagnosis, management, and outcome.

Fetal ovarian cysts are the most common abdominal cysts observed in the female fetus but may be mistaken for genitourinary cysts, gastrointestinal cysts, lymphangiomas, or fetus in fetu. Ultrasonography (US) is the imaging modality of choice for fetal assessment, and magnetic resonance imaging is a useful problem-solving tool when uncertainty remains after careful US evaluation. At US, a fetal ovarian cyst manifests as an anechoic thin-walled cyst superior and parasagittal to the bladder. A daughter cyst may occasionally be observed and is pathognomonic for a cyst of ovarian origin. Fetal ovarian cysts may be simple or complicated and unilateral or bilateral, and they may masquerade as a solid mass when hemorrhage or torsion occurs. Complicated cysts may exhibit multiple septations, fluid-fluid levels, or mobile internal echoes. It is important to differentiate a hemorrhagic ovarian cyst from solid abdominal neoplasms that may be seen in a fetus. Recognition of the pertinent imaging findings will help radiologists distinguish fetal ovarian cysts from other fetal intra-abdominal masses in the differential diagnosis. Malignant ovarian neoplasms are rare in the fetus and neonate and thus are not considered in the differential diagnosis. The current literature on the management and outcome of fetal ovarian cysts is reviewed, with imaging studies presented from the authors' practice. Most fetal ovarian cysts resolve spontaneously; if operative intervention is required, the goal should be ovarian preservation.

Hypoxia disruption of vertebrate CNS pathfinding through ephrinB2 Is rescued by magnesium.

The mechanisms of hypoxic injury to the developing human brain are poorly understood, despite being a major cause of chronic neurodevelopmental impairments. Recent work in the invertebrate Caenorhabditis elegans has shown that hypoxia causes discrete axon pathfinding errors in certain interneurons and motorneurons. However, it is unknown whether developmental hypoxia would have similar effects in a vertebrate nervous system. We have found that developmental hypoxic injury disrupts pathfinding of forebrain neurons in zebrafish (Danio rerio), leading to errors in which commissural axons fail to cross the midline. The pathfinding defects result from activation of the hypoxia-inducible transcription factor (hif1) pathway and are mimicked by chemical inducers of the hif1 pathway or by expression of constitutively active hif1α. Further, we found that blocking transcriptional activation by hif1α helped prevent the guidance defects. We identified ephrinB2a as a target of hif1 pathway activation, showed that knock-down of ephrinB2a rescued the guidance errors, and showed that the receptor ephA4a is expressed in a pattern complementary to the misrouting axons. By targeting a constitutively active form of ephrinB2a to specific neurons, we found that ephrinB2a mediates the pathfinding errors via a reverse-signaling mechanism. Finally, magnesium sulfate, used to improve neurodevelopmental outcomes in preterm births, protects against pathfinding errors by preventing upregulation of ephrinB2a. These results demonstrate that evolutionarily conserved genetic pathways regulate connectivity changes in the CNS in response to hypoxia, and they support a potential neuroprotective role for magnesium.

The interactions of antimicrobial peptides derived from lysozyme with model membrane systems.

Two peptides, RAWVAWR-NH2 and IVSDGNGMNAWVAWR-NH2, derived from human and chicken lysozyme, respectively, exhibit antimicrobial activity. A comparison between the L-RAWVAWR, D-RAWVAWR, and the longer peptide has been carried out in membrane mimetic conditions to better understand how their interaction with lipid and detergent systems relates to the reported higher activity for the all L-peptide. Using CD and 2D 1H NMR spectroscopy, the structures were studied with DPC and SDS micelles. Fluorescence spectroscopy was used to study peptide interactions with POPC and POPG vesicles and DOPC, DOPE, and DOPG mixed vesicle systems. Membrane-peptide interactions were also probed by ITC and DSC. The ability of fluorescein-labeled RAWVAWR to rapidly enter both E. coli and Staphylococcus aureus was visualized using confocal microscopy. Reflecting the bactericidal activity, the long peptide interacted very weakly with the lipids. The RAWVAWR-NH2 peptides preferred lipids with negatively charged headgroups and interacted predominantly in the solvent-lipid interface, causing significant perturbation of membrane mimetics containing PG headgroups. Peptide structures determined by 1H NMR indicated a well-ordered coiled structure for the short peptides and the C-terminus of the longer peptide. Using each technique, the two enantiomers of RAWVAWR-NH2 interacted in an identical fashion with the lipids, indicating that any difference in activity in vivo is limited to interactions not involving the membrane lipids.